Three\nStrikingly Different Crystal Habits of Tadalafil:\nDesign, Characterization, Pharmaceutical Performance, and Computational\nStudies

The present study aims at improving the physicochemical\nproperties\nof a widely used drug Tadalafil through crystal habit modification,\nwithout changing the polymorphic form. Three distinct types of crystal\nhabits, namely, needle, plate, and block, were obtained under controlled\ncrystallization protocols with optimized solvent compositions. Complete\ncharacterization of these three crystal habits was carried out using\npowder X-ray diffraction, differential scanning calorimetry, thermogravimetric\nanalysis, and Fourier transform infrared spectroscopy. Morphological\nfeatures were studied by optical and scanning electron microscopy.\nEvaluation of the pharmaceutical performance of different crystal\nhabits reveals significant improvement in compressibility and flow\nproperties for the block-shaped crystals in comparison to the needle-\nand plate-shaped crystals. Also, a more linear tablet compression\nbehavior was noted for the plate and block morphologies of the API\ncompared to their needle counterpart. <i>In vitro</i> dissolution\nstudies showed distinct release profiles for the same API form with\ndifferent crystal habits, i.e., needle > plate > block. Insights\ninto\ncrystal growth mechanism and the role of solvents in affording the\nobserved crystal habits are presented based on molecular dynamics\nsimulations of intermolecular interactions with crystal facets, in\nconjunction with the experimental crystal face indexing of the single\ncrystals of different habits. These observations were further supported\nby interaction topology analysis and the electrostatic features on\ndifferent crystal facets.